Structure and Anti-Inflammatory Activity of a New Unusual Fucosylated Chondroitin Sulfate from Cucumaria djakonovi

摘要

Fucosylated chondroitin sulfate >CD was isolated from the sea cucumber Cucumaria djakonovi collected from the Avachinsky Gulf of the eastern coast of Kamchatka. Structural characterization of >CD was performed using a series of non-destructive NMR spectroscopic procedures. The polysaccharide was shown to contain a chondroitin core [→3)-β-d-GalNAc-(1→4)-β-d-GlcA-(1→]n where about 60% of GlcA residues were 3-O-fucosylated, while another part of GlcA units did not contain any substituents. The presence of unsubstituted both at O-2 and O-3 glucuronic acid residues in a structure of holothurian chondroitin sulfate is unusual and has not been reported previously. Three different fucosyl branches Fucp2S4S, Fucp3S4S and Fucp4S were found in the ratio of 2:1:1. The GalNAc units were mono- or disulfated at positions 4 and 6. Anti-inflammatory activity of >CD was assessed on a model of acute peritoneal inflammation in rats. About 45% inhibition was found for >CD, while a structurally related linear chondroitin sulfate >SS from cartilage of the fish Salmo salar demonstrated only 31% inhibition, indicating that the presence of sulfated fucosyl branches is essential for anti-inflammatory effect of chondroitin sulfates of marine origin.